Anal Fissure: Symptoms, Diagnosis and Treatment : Symptoms, Diagnosis and Treatment [1 ed.] 9781620817117, 9781612097169

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Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Anal Fissure: Symptoms, Diagnosis and Treatment : Symptoms, Diagnosis and Treatment, Nova Science Publishers,

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Anal Fissure: Symptoms, Diagnosis and Treatment : Symptoms, Diagnosis and Treatment, Nova Science Publishers,

PUBLIC HEALTH IN THE 21ST CENTURY

ANAL FISSURE

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SYMPTOMS, DIAGNOSIS AND TREATMENT

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Anal Fissure: Symptoms, Diagnosis and Treatment : Symptoms, Diagnosis and Treatment, Nova Science Publishers,

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PUBLIC HEALTH IN THE 21ST CENTURY

ANAL FISSURE

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SYMPTOMS, DIAGNOSIS AND TREATMENT PIERPAOLO SILERI AND

ACHILLE LUCIO GASPARI EDITORS

Nova Science Publishers, Inc. New York Anal Fissure: Symptoms, Diagnosis and Treatment : Symptoms, Diagnosis and Treatment, Nova Science Publishers,

Copyright © 2012 by Nova Science Publishers, Inc. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: Telephone 631-231-7269; Fax 631-231-8175 Web Site: http://www.novapublishers.com

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Library of Congress Cataloging-in-Publication Data Anal fissure : symptoms, diagnosis and treatment / editors, Pierpaolo Sileri and Achille Lucio Gaspari. p. ; cm. Includes bibliographical references and index.

ISBN:  (eBook)

1. Anus--Diseases. 2. Anus--Diseases--Treatment. I. Sileri, Pierpaolo. II. Gaspari, Achille. [DNLM: 1. Fissure in Ano--therapy. 2. Fissure in Ano--diagnosis. WI 605] RC866.A53 2011 616.3'5--dc22 2011009052

Published by Nova Science Publishers, Inc. †New York Anal Fissure: Symptoms, Diagnosis and Treatment : Symptoms, Diagnosis and Treatment, Nova Science Publishers,

CONTENTS

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Preface

vii

List of Contributors

ix

Chapter 1

Anal Canal: Anatomy and Phisiopathology Michele Grande

1

Chapter 2

Chemical Sphincterotomy Giovanni Milito and Federica Cadeddu

29

Chapter 3

Botulinum Toxin and Anal Fissure Oliver Jones

47

Chapter 4

Current Surgical Management of Anal Fissure Jason W. Allen and Herand Abcarian

63

Chapter 5

Postoperative Complications after Treatment for Chronic Anal Fissure Giovanni Milito, Federica Cadeddu and Ilaria Ciangola

Chapter 6

Anal Fissure: Treatment Options in Particular Cases Stefano D’Ugo, Sara Di Carlo, Lodovico Patrizi and Vito Maria Stolfi

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91

vi Chapter 7

Contents Conservative and Surgical Treatment of Chronic Anal Fissure: Longer-Term Results from our Prospective Database Pierpaolo Sileri, Luana Franceschilli, Giulio P. Angelucci, Sara Lazzaro, Alessandra Di Giorgio, and Achille L. Gaspari

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Index

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123

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PREFACE Anal fissure is a common problem with a prevalence in the general population around 2%. However this rate is underestimated, being probably as high as 15%, since most symptomatic patients do not seek medical attention and prefer selftreatments usually erroneous secondary to misdiagnosis. The presence of an anal fissure is reliably associated with an elevated intra-anal pressure and decreased blood flow to the anoderm. Symptoms include pain, bleeding, pruritus, and soiling. Greater than 90% of acute anal fissures are of short duration and heal spontaneously or with simple measures. A high-fiber diet with an increased intake of water is recommended, laxatives may be used when required to make soft constipated stool and warm sitz baths may offer symptomatic relief. Acute fissures that fail to heal become chronic fissures, which have traditionally been treated by surgery. Traditionally, lateral internal sphincterotomy has been considered the gold standard treatment for chronic fissures, but this procedure requires anaesthesia and is associated with a noteworthy risk of incontinence. More recently, various pharmacologic agents have been shown to decrease resting anal pressure and promote fissure healing. This so-called chemical sphincterotomy has been used as first-line treatment for chronic anal fissure in many centres. The authors of this book review and discuss recent developments on anal fissure conservative medical and surgical treatment as well as the management of surgical complications. This books, through the personal experience of all contributors, offers a complete guide to general practitioner, resident and medical student who frequently face with difficult questions concerning the optimum management of anal fissure.

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LIST OF CONTRIBUTORS Herand Abcarian Professor of Surgery University of Illinois at Chicago, Chicago, IL, US

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Jason W. Allen Clinical Fellow, Surgery University of Illinois at Chicago, Chicago, IL, US Giulio Paolo Angelucci Research Yellow, Surgery University of Rome Tor Vergata, Rome, Italy Ilaria Ciangola Resident in General Surgery University of Rome Tor Vergata, Rome, Italy Federica Cadeddu Assistant Professor of Surgery University of Rome Tor Vergata, Rome, Italy Stefano D‘Ugo Resident in General Surgery University of Rome Tor Vergata, Rome, Italy Sara Di Carlo Resident in General Surgery University of Rome Tor Vergata, Rome, Italy

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List of Contributors Luana Franceschilli Clinical Fellow, Colorectal Surgery University of Rome Tor Vergata, Rome, Italy Michele Grande Assistant Professor Surgery University of Rome Tor Vergata, Rome, Italy Oliver Jones Consultant Surgeon John Radcliffe Hospital, Oxford, United Kingdom Sara Lazzaro Research Fellow, Surgery University of Rome Tor Vergata, Rome, Italy

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Giovanni Milito Associate Professor of Surgery University of Rome Tor Vergata, Rome, Italy Lodovico Patrizi Assistant Professor of Gynecology and Obstetrics University of Rome Tor Vergata, Rome, Italy Vito Maria Stolfi Associate Professor Surgery University of Rome Tor Vergata, Rome, Italy

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In: Anal Fissure Editors: P. Sileri and A. L. Gaspari

ISBN: 978-1-61209-716-9 © 2012 Nova Science Publishers, Inc

Chapter 1

ANAL CANAL: ANATOMY AND PHYSIOPATHOLOGY Michele Grande University of Rome Tor Vergata, Rome, Italy

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ANATOMY The Anal Canal The term "anal canal" was proposed by Symington in 1888 to indicate the portion "perineal" rectum, limited by the pelvic floor up and anal orifice down [1]. This definition corresponds to that given by Morgan and Thompson (1956) of surgical anal canal, extended from anorectal ring to the anal margin, which differs from the anatomical anal canal, between the dentate line and anal margin [2]. The dentate line, located at the midpoint or middle third of the union with the lower third of the internal sphincter, it refers to the line of anal valves [3]. These valves, semilunar in appearance, sometimes papillary, connect the base columns of Morgagni, arranged into 6-10 vertical folds, with circumferential distribution around the lumen of the anal canal [4], which are particularly evident to just below the midpoint of the anal canal, gradually disappearing at the upper end of that. Opening into these crypts are a variable number of anal glands that traverse the submucosa to enter the internal sphincter and terminate in the intersphinteric plane, exocrine structures that cross the internal sphincter, in some cases reach the intersphinteric plane, and help to lubricate the anal canal [5]. Among the many

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synonyms used to indicate the line of anal valves (pectinate line, the line of crypts, papillary line, line ano-cutaneous, muco-cutaneous junction, anorectal line) the term of the dentate line seems to be the most correct, its approximate distance from the anal margin is about 2 cm [6,7, 8,9,10,11]. The term "anorectal ring‖ was introduced by Milligan and Morgan (1934) to indicate to this muscular ring at the junction of the rectum with the anal canal, very important from a functional point of view; consist of internal sphincter completed by muscle puborectal for the upper half and the external sphincter for the lower half. Between internal and external sphincter is inter-sphincteric space with the longitudinal layer (Figure 1) [3,12].

Figure 1. Schematic representation of the anal sphincter.

The anal margin is defined as the point at which the walls of the anal canal come into contact in their normal resting position. If the histological anal canal extends from top to the bottom of internal sphincter inside a length of about 3 cm, in living anorectal ring distance from the anal margin (anal orifice) is about 4 cm [7,13,14]. It is therefore appropriate, taking into account the influence of fixation procedures on real measures of histological samples, to match approximately the anal margin to intersphincteric groove, between the edge of the internal sphincter muscle and the distal portion (subcutaneous) of the external sphincter, near which there is the passage from epithelium of the anal canal to the perianal skin [10]. Although the term of ano-cutaneous line, synonymous board or anal margin, may, according to some authors, give rise to confusion in clinical practice is widely used [15,8,10]. The anal orifice in males is behind the line of ischial spine, at 20-25 mm from apex of the coccyx, while in woman is more superficial and coincides with line of ischial spine, at 25-30 mm from apex of the coccyx [16]. Histologically, the anal canal has a variable lining. The mucosa of the upper anal canal, like that of the rectum, is lined by columnar epithelium. There is a

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transitional or cloacogenic zone where the mucosa consists of layers of cuboid cells interspersed with tongues of columnar epithelium. The mucosa distal to the dentate line is lined by squamous epithelium devoid of hair and glands [17]. At the anal verge, the lining acquires the characters of normal skin with its apocrine glands. The area with transitional epithelium has been shown over time with different names (mucosal zone, middle zone, cloacal region, hemorrhoidal zone, transitional zone), the term "anal transitional zone‖ (ATZ), recently introduced, seems to be better corresponding to its characteristics: this is indeed an area interposed between a colorectal mucosa proximal and squamous epithelium distally. Its extension is variable: from a few millimeters to 2 cm above (usually 1 cm) and a few millimeters to ½ cm below the dentate line. In ATZ may contain areas of squamous epithelium, simple columnar or colorectal cryptic, melanocytes and endocrine cells, Paneth cells, islands of pyloric metaplasia and gastric mucosa of fundic type; frequently the epithelium of ATZ consists of cells can be columnar, cuboidal, polygonal and flat arranged in 4-9 layers [8]. The anal canal, surrounded by levator ani and sphincters, is connected posteriorly to the apex of the coccyx and the raphe or ligament anococcigeo. This ligament, tense between the rear of the anal canal and the coccyx, is formed from the crossing of fibers from both sides of the elevator and below the confluence of the external sphincter fibers that are attached to the coccyx [18]. Lateral to the external sphincter lies the ischioanal space. The triangular ischioanal space is bordered superiorly by the levator ani muscle. Posteriorly, the most caudal space is the superficial postanal space that terminates at the coccyx. Above the superficial postanal space is the anococcygeal ligament, and deep to this ligament, but below the levator ani muscle is the deep postanal space (space of Courtney) (Figure 2). This space is continuous laterally with each ischioanal space and when infected can create a large ‗‗horseshoe‘‘ abscess. Above the levator ani, below and posterior to the rectum, and anterior and superior to the sacrum is the supralevator space that can extend into the retroperitoneum (17). Before the anal canal in males is related with the tendinous center of perineum, the urogenital diaphragm that contains the membranous portion of the urethra and the bulbous urethra; in women with perineal body and posterior vaginal wall. The mucosa of the anal canal that extends above the dentate line adheres loosely to the underlying muscle (internal sphincter) interposing between the two structures submucosal space containing the internal hemorrhoidal plexus, which continues proximally with the submucosa of the rectum. This space is limited below by the suspensory ligament of Parks, located at the halfway down the anal

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canal, composed of fibers that, coming from the internal sphincter and the muscularis mucosae is set at the level of the crypts, the lining of the anal canal causing a strong anchored to the surface muscle [19].

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Figure 2. Postanal space: sagittal section. 1, superficial postanal space; 2, deep postanal space (space of Courtney).

Anal sphincter continence involving three muscles: internal sphincter (involuntary), external sphincter (voluntary) and levator ani. A recent study of 20 normal subjects showed, by using three-dimensional endoanal ultrasonography, that there are differences between the sexes regarding the anatomy sphincter [20]. The anal canal was longer in males (32.6 ± 5.3 mm) than in women (25.1 ± 3.4mm, P = 0.001). Similarly, in the male internal anal sphincter was found to be longer (25.6 ± 6.3 mm) than in women (19.8 ± 4.0 mm, P = 0.02), even if the length of the internal sphincter as percentage of the total length of the anal channel did not show differences in both sexes (78.3 ± 8.2% and 78.7 ± 9.0% in male and female, respectively, P = 0.91). The internal sphincter is not merely a thickened extension of the circular smooth muscle layer surrounding the colon. Indeed, in dogs, the rectal circular muscle layer is tightly packed with poorly defined septa while the internal anal sphincter contains discrete muscle bundles separated by large septa [21]. In the rectum, the interstitial cells of Cajal (ICC) are organized in dense networks along the submucosal and myenteric borders. In the internal anal sphincter, the ICCs are located along the periphery of the muscle bundles within the circular layer [21]. The internal sphincter extend up to a length of about 3 cm and have a thickness between 2 and 8 mm [22]; its lower limit is about 6-8 mm anal orifice [3,23]. It is innervated by fibers of the autonomic nervous system and delivering with its involuntary contraction continence.

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The inter-sphincteric space is a thin fat-containing space with variable thickness: it may be hard to discern in some and easily visible in others. The intersphincteric space contains the longitudinal layer (also named longitudinal muscle), which is the continuation of the smooth muscle longitudinal layer of the rectum. The longitudinal layer receives contributions from the levator ani, particularly the puboanalis, and a large fibro-elastic element derived from the endopelvic fascia. The longitudinal layer is 2.5 mm thick and the thickness decreases with age. Cranially the layer is predominantly muscular while fibroelastic caudally. The fibro-elastic tissue of the longitudinal layer is continuous with the fibro-elastic network outside the sphincter to the perianal skin to form the corrugator cutis ani, thereby forming an intra-sphincteric fibro-elastic network passing through the external sphincter [24]. Shafik supports a different morphological organization of the anal longitudinal muscle. The author believes that this muscle is composed of three layers separated by fascial septa: the medial layer is an extension of the longitudinal muscle of the rectum, the intermediate is an extension of the elevator ani (pubococcygeus muscle) while the lateral, present only in the lower part of the anal canal, is an extension of the deep portion of the external sphincter. At the lower internal sphincter these three layers form a common central tendon from which branch off some fibers crossing the distal portion ( subcutaneous) of the external sphincter and, below it, are attached on the perianal skin to form the corrugator cutis ani [3,8,25]. The external sphincter consists of striated muscle fibres, and according to recent studies also a component of smooth muscle, surrounding an elliptical or circular course the anal canal, lateral to the internal sphincter muscle and the muscle longitudinal [26]. The external sphincter is approximately 2.7 cm high, but is anteriorly shorter in women (approximately 1.5 cm) [3]. The lateral part of the external sphincter is approximately 2.7 cm high. The external sphincter has a thickness of 4 mm on endoluminal imaging [24] . MRI studies have made clear that the external sphincter forms the lower outer part of the anal sphincter and the puborectalis the upper outer part [24]. Number of its components, two (superficial and deep) [27,28,29,30] or three (one subcutaneous, superficial and deep) is still discussed [12,15]. An interesting theory of functional organization of the external sphincter in three slings muscle action opposed was proposed by Shafik. The external sphincter is considered to have three muscle groups willing to sling around the anal canal, these slings, proceeding in the craniocaudal may display a convexity respectively front, rear and then front again. The upper muscle group would be composed by the deep layer of the sphincter and bundles puborectal, attached

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below to the pubis. The intermediate group was constituted by the surface layer of the sphincter, anchored to the dorsal surface of the apex of the coccyx. The third identified with the sling portion subcutaneously, anchored before the perianal skin and crossed by longitudinal muscle fibres (Figure 3) [31].

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Figure 3. Schematic representation of triple tie of Shafik.

Theories Shafik, very interesting, have been subject to criticism, and have not been confirmed in subsequent studies [3,7,32,33]. Currently it is considered that the external sphincter has posterior fibres continuous with the anococcygeal ligament, some of the anterior fibres decussate into the superficial transverse perineal muscles and perineal body. The deep part of the external sphincter is intimately related to the puborectalis [24]. Lateral to the external sphincter lays the ischioanal space. The triangular ischioanal space is bordered superiorly by the levator ani muscle. Posteriorly, the most caudal space is the superficial postanal space that terminates at the coccyx. Above the superficial postanal space is the anococcygeal ligament, and deep to this ligament, but below the levator ani muscle is the deep postanal space (space of Courtney). This space is continuous laterally with each ischioanal space and when infected can create a large ‗‗horseshoe‘‘ abscess. Above the levator ani, below and posterior to the rectum, and anterior and superior to the sacrum is the supralevator space that can extend into the retroperitoneum [17].

Pelvic Floor Muscles The levator ani separates the pelvic cavity from the perineum and performs the dual function of supporting the visceral organs and maintaining continence. It originates from the posterior surface of the superior pubic rami bilaterally and

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attaches to the inner surface of the ischium. Traditionally the levator ani muscle has been thought to consist of 3 muscles: (1) the iliococcygeal muscle, (2) the pubococcygeal muscle, and (3) the puborectalis muscle. 



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

The iliococcygeus arises from the posterior half of the tendineus arc inserting into the last two segments of the coccyx and the midline anococcygeal raphe. The anococcygeal raphe is the interdigitation of the iliococcygeal fibres from both sides and extends from the coccyx to the anorectal junction. The iliococcygeus forms a sheet-like layer and is often largely aponeurotic. Carries a support on the back of the anal canal, without contracting a direct relationship with the rectal wall; The pubococcygeus arises from the anterior half of the tendineus arc and the periosteum of the posterior surface of the pubic bone at the lower border of the pubic symphysis, its fibres directed posteriorly inserting into the anococcygeal raphe and coccyx; The puborectalis forms a U-shaped sling around the urogenital hiatus. Contraction of the puborectalis lifts and compresses the urogenital hiatus. The puborectalis is the main part of this muscle and goes around the upper part of the anus where it is attached posteriorly to the anococcygeal ligament. During vaginal delivery the levator ani muscle is substantially stretched and injury may occur, often near the pubic bone insertion [27,29].

According to recent interpretations levator ani is formed by iliococcygeus and pubococcygeus, while puborectal be considered as part of the deep portion of the external sphincter, both are supplied by the pudendal nerve [34,35]; on the contrary electrophysiological studies indicate a direct innervation by branches sacral (S3 and S4), and recent anatomical studies (which in this innervation from the pelvic side include fibers from S2), argue against the thesis of the puborectal innervation by the pudendal nerve [36,37,38] . To mention the coccygeus muscle that forms the posterior part of the pelvic diaphragm. This shelf-like triangular musculotendinous structure has its origin at the ischial spine and courses along the posterior margin of the internal obturator muscle. The muscles inserts at the lateral side of the coccyx and the lowest part of the sacrum. The sacrospinous ligament is at the posterior edge of the coccygeus muscle and is fused with this muscle. The proportions of the muscular and ligamentous parts may vary. The coccygeus is not part of the levator ani, having a different function and origin. The coccygeus muscle is innervated by the third and fourth sacral spinal nerves on its superior surface (24).

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Unlike other striated muscles the elevator ani has resting electric activity. Recent studies have suggested that this activity might be a function of intraabdominal pressure and visceral weight. The activity increase in the erect compared to the recumbent position, and upon elevation of intra-abdominal pressure [39]. The cause of this myoelectric activity is not precisely known, but has been suggested to be related to the presence (in the cadavers) of smooth muscle bundles in the elevator ani [39]. Smooth muscle bundles begin to appear at the lateral part of the elevator ani and gradually increase medially, so that the medial part of the muscle is formed of two layers: deep (pelvic), consisting of smooth muscle bundles, and superficial (perineal) consisting of skeletal fibers. The connective tissue separating the layers serves not only to bind the muscle layers, but seems also to provide a pathway for a neurovascular bundle that supplies the elevator ani muscle.

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Arterial Supply The vascularization of the rectum and anal canal depends by superior, middle and lower rectal (hemorrhoidal) arteries with the contribution of small branches of the middle sacral artery and transverse perineal artery [40]. The inferior mesenteric artery, to the junction with the left common iliac vessels, according to some authors [3, 7,15] or distal to the last sigmoid artery according to other changes the name in superior rectal artery [6,16]. The final branch of the aorta before its bifurcation, descending into the mesorectum with the presacral nerve, terminates inferiorly in the upper portion of the posterior wall of the rectum at the level of the third sacral vertebra where it divides into two branches, right and left. This supplies the rectum and the upper third of the anal canal (Figure 4) [17]. It‘s possible that by the superior rectal artery origins third median branch called dorsal hemorrhoidal artery or azygous rectum [16]. In some cases the superior rectal artery can be replaced by more arterial branches that arise directly from inferior mesenteric artery distal sigmoid artery [16]. The superior rectal artery main branches divide further into smaller branches that penetrate in the submucosa about 8 cm from the anal margin, and shall run vertically, reach the columns of Morgagni, ending in a capillary plexus at level of the anal valves [41,42]. Some small terminal branches form anastomoses with the submucosal hemorrhoidal plexus other small branches attributable to the superior rectal artery be opened without the interposition of capillaries in the vascular space called the corpus cavernosum of the rectum [43].

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Figure 4. Schematic representation of the vascularization of the rectum and anus. 1, inferior mesenteric artery; 2, left colic artery; 3, sigmoid arteries; 4, superior hemorrhoidal artery; 5, hypogastric artery; 6, middle hemorrhoidal artery; 7, internal pudendal artery; 8, inferior hemorrhoidal artery.

The middle rectal (hemorrhoidal) arteries, originating from the internal iliac arteries, supply to distal rectum and proximal anal canal. The presence of these arteries is variable. The inferior rectal (hemorrhoidal) arteries arise from the internal pudendal artery, which is a branch of the internal iliac artery. These arteries traverse the ischioanal fossa on both sides of the anal canal feeding the sphincter muscles. Intramural collaterals exist between the superior and inferior rectal arteries at the level of the dentate line in the submucosa. This accounts for the low incidence of rectal ischemia [42]. According to a recent study intramural anastomoses exist only between superior and lower rectal artery in the submucosa at the level of dentate line [44]. Unlike the small intestine and colon, which showing on the wall antimesenteric a reduced vascularization and an organization in intramural arterial

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arches, the arterial network of the rectum is homogeneous and the terminal branches being straight is running for the most part obliquely [42].

Venous Drainage The veins that drain the rectum and anal canal have a course similar to that of the corresponding arteries. The superior rectal veins tributaries of the portal system via the inferior mesenteric vein, draining the rectum and upper anal canal. The lowermost portion of the rectum and the anal canal drain into the internal iliac veins directly through the middle rectal veins and the inferior rectal veins (via the pudendal vein) [17].

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Lymphatic Drainage Much of the lymphatic drainage of the anal canal and rectum follows the arterial supply. The rectum drains via the superior rectal lymphatics to the inferior mesenteric lymph nodes in the retroperitoneum and laterally to the internal iliac nodes along the middle and inferior rectal vessels through the ischioanal fossa. Lymph drainage from below the dentate line drains to the inguinal nodes. The study of lymphatic drainage in normal anatomy of the rectum revealed the rectal drainage via the superior rectal and inferior mesenteric vessels to the lumboaortic nodes that have no communication with to the internal iliac nodes. However, if distal obstruction occurs, drainage can occur from the anal canal to the superior rectal nodes or laterally to the ischioanal fossa [17].

Innervation The anorectum and pelvic floor are supplied by sympathetic, parasympathetic and somatic fibres [21]. Sympathetic preganglionic fibres originate from the first 3 lumbar segments of the spinal cord are responsible for innervation of the rectum. After leaving the lumbar region, they join at the preaortic plexus and extend caudally from the aortic bifurcation toward the mesenteric plexus before reaching the level of the upper rectum. It then bifurcates into the left and right branches, traveling down both sides of the pelvis before joining the parasympathetic nerve branches. The parasympathetic nerve supply originates from the caudal 3 sacral nerve roots,

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which form the nervi erigentes. The fibers then rapidly progress anteriorly, joining the sympathetic fibers to create the pelvic plexus. The pelvic plexus is located laterally and superior to the levator ani muscle in the mid portion of the lateral stalk. The pelvic plexus then feeds the urinary and genital organs and the rectum with both parasympathetic and sympathetic fibers (Figure 5) [21].

Figure 5. Schematic representation of the pelvic plexus.

The pelvic plexus also supplies the periprostatic plexus that is important for sexual function in men [45]. In women, the hypogastric plexus composed of sympathetic nerve fibers pass through the uterosacral ligament near the rectum. In men, these fibers pass adjacent to the anterolateral wall of the rectum in the retroperitoneal tissue. The pudendal nerves arise from the caudal 3 sacral nerve roots. The nerves cross the ischial tuberosity in the lateral wall of the ischioanal fossa bilaterally. It branches into the inferior rectal, perineal, and dorsal nerves of the penis or clitoris [17,45]. The anal canal also receives innervation from both sympathetic and parasympathetic fibers. Both inhibit the internal anal sphincter. The external sphincter relies on innervation from the perineal branch of the fourth sacral nerve

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and the inferior rectal branch of the internal pudendal nerve. As previously mentioned, the levator ani muscle is innervated by branches of the pudendal, inferior rectal, perineal, and sacral (S3 and S4) nerves [46]. Sensation of the anal canal comes from the inferior rectal nerve, also a branch of the pudendal nerve. The epithelium of the anal canal is extensively innervated up to 2 cm proximal to the dentate line [17]. The myenteric plexus (Auerbach) along with the submucosal (Meissner) form innervation "intrinsic" or enteric plexus. This consists of groups of nerve cells that are located between the circular and the longitudinal muscle layer (Auerbach's plexus) and in the submucosa (Meissner's plexus) from esophagus to the rectum and the anal canal, until the transition zone, below it disappears completely. In the enteric plexus terminating fibers "extrinsic" sympathetic and parasympathetic [23,41]

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ANAL SPHINCTER TONE AND REFLEXES The study of the function of anal sphincters and pelvic floor has been a major boost in recent years, partly due to increased interest in anorectal disease and partly to developments in surgical techniques, which today can significantly reduce the possibility of a colostomy definitive [47]. Fecal continence and defecation are dependent on several neurological and anatomical factors that involve coordinated physiological processes, including intestinal transit and absorbition, colic transit, rectal compliance, expulsion force and coordinated pelvic floor function [48]. Moreover anal continence relies upon the ability of the anorectum to discriminate between the states of fecal matter, solid, liquid, or gas. Its presence also depends on both voluntary and involuntary control and a multitude of other factors, adding to its complexity [17]. The function of reservoir is instead attributable to the adaptability of the rectum with faecal increasing volumes without endorectal pressure increases proportionally. This is possible thanks to the considerable distensibility of the rectum, the result of its structure and properties of highly flexible arrangement of the component muscle relaxing two new volumes. In fact, after initial and rapid increase in intraluminal pressure, probably due to a reflex contraction of the rectal muscles, we see a sharp decrease in pressure which becomes constant in relation to the coefficient of elasticity parietal [49]. Depending on the degree of rectal distension sensitivity changes from its initial filling sensation (sensation first) becomes a constant feeling that lasts about 30 seconds (constant sensation), since to achieve a feeling of urgent need to defecate (maximum tolerable volume). The

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measurement of volumes and pressures endorectal, measured at those feelings, offers an index of rectal distensibility calculated by Arhan and colleagues by measuring the relationship between stool volume and pressure (compliance) [50]. The smooth muscle internal anal sphincter is formed by a thickening of the circular muscle layer of the rectum [47,51]. The internal muscle layer of the rectum, the circular, which is in direct continuation with the circular muscle of the sigmoid, distally, specializes in the formation of internal anal sphincter, at the pectinate line for a distance of about 2-3 cm occupies a thickness of 0.5-1 cm. Longitudinal muscle layer, however, is to operate and to break down the fibers of the internal and external sphincters, the so-called longitudinal muscle intersphincteric. The muscle is innervated by sympathetic and parasympathetic fibers from the intramural non-adrenergic, cholinergic, but neither type purinergic or peptidergic. The sympathetic innervation is through hypogastric nerves and originates from the fifth lumbar segment. This innervation is considered important in maintaining basal tone pressure; denervation reduces, but does not abolish, the contractile activity of the internal anal sphincter, which is therefore also reflect intrinsic myogenic activity. The parasympathetic innervation is supplied by fibers passing through the S2-S4 sacral plexus to the pelvic plexus before and then seem to have little importance in the basal tone while inducing a mild relaxation of internal anal sphincter [52,53] Duthie and Watts first showed that the intra-anal pressure at rest (by measuring the pressure before and after administration of a releasing muscle) is primarily due to the action of the anal sphincter internal 10. The other contributors to anal resting tone include the external anal sphincter, the anal mucosal folds and the puborectalis muscle. Penninckx et al. estimated that anal resting tone was generated by nerve-induced activity in the internal sphincter (45% of anal resting tone), myogenic tone in the internal sphincter (10%), the external sphincter (35%) and the anal hemorrhoidal plexus (15%) [55]. These figures should be regarded as estimates, because they were obtained, in part, from complex studies, moreover the relative contributions of these factors to anal resting tone are influenced by several factors [21]. This activity sphincter basal or basal tone, it creates a high pressure zone that extends about 4 cm from the ano-cutaneous line up to about 11.5 cm above the pectinate line and the peak pressure which is recorded at about 2.5 cm from the line itself. The adjustable pressure within the anal canal, while showing large individual variations (25 to 80 cm H2O), is still significantly higher than those prevailing in the rectum during the resting phase (2-5 cm H2O), this difference is called the anorectal pressure gradient [56,57,58].

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Postural changes and other increases in intra-abdominal pressure such as sneezing, coughing, and the Valsava maneuver increase the resting tone of the external sphincter by an anal reflex. The second sacral spinal segment modulates the external sphincter, which can be contracted voluntarily for 40 to 60 second periods [17]. Lower the contribution of the external anal sphincter tone at baseline: in fact, blockade of bilateral pudendal nerves that innervate the external anal sphincter results in a reduction of only 16-20% of muscle tone at rest [59]. Anal resting pressure is not stationary but varies during the day. In addition to spontaneous relaxation of the internal sphincter, circadian variations that are dependent on the sleep-wake cycle and ultradian (~20-40 min in length) rhythms that are independent of the sleep-awake cycle have also been described [21]. These rhythmic oscillations are distinct in contractions of prolonged duration with average frequency of 12.2/min and ultraslow with average frequency of 2.6/min. Anal relaxation induced by rectal distention (recto-anal inhibitory reflex, RAIR) is mediated by intrinsic nerves, physiologically arrival of the fecal mass in the rectum results in a reduction of the pressure existing in the upper portion of the anal canal. As a consequence of the latter, the waste moves further down and comes into contact with receptors in the upper part of the anal canal. The receptors determine the quality of the content (the sampling reflex). If the time is right for defecation, impulses are sent to further contract the rectal muscles, relax the external sphincter and the pelvic floor with the puborectalis sling, to facilitate defecation. If defecation has to be suppressed, a voluntary contraction of the external sphincter and pelvic floor, using the puborectalis sling, propels the luminal contents back up again above the rectum and the urge to defecate ceases. The mechanism of accommodation is guided by spinal reflexes controlled by the cerebral cortex. The first stimulus to defecation occurs in the presence of a volume of approximately 25% of the maximum tolerable, from a filling of 150 ml, the internal sphincter does not take its tone and thus remains in a state of relaxation. Approximately for 350 ml also the tonic activity of the external sphincter is inhibited and continence can be maintained even for a short time with the activity of phasic voluntary contraction. Under normal conditions, therefore, the internal anal sphincter is in a state of partial contraction and release the response to rectal distension (recto-sphincteric reflex). This tonic contraction partially regulated by a prevailing myogenic component, is supported and modulates by sympathetic, that from V lumbar segment reaches the sphincter through the hypogastric nerves. In histological preparations of the smooth sphincter contraction is mediated by α-adrenergic receptors and released from β [60].

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The first population of receptors is predominant, so that the contractile response to noradrenaline can be converted into relaxation when selectively block α-receptors. Acetylcholine, in contrast, by the action on muscarinic receptors shows a predominantly inhibitory effect. External anal sphincter and pelvic floor muscles show electrical activity at rest (action potentials recordable EMG), this capacity is maintained at subconscious during sleep and varies during position changes. This electrical activity is greater in the upright posture [21]. The anatomical substrate of this function is given by the two types of muscle fibres constituting the striated sphincter apparatus, type 1 fibers suitable for tonic contractions (fatigue resistant, slow twitch) and type 2 fibers suitable for rapid contractions. The fibers distribution favours tonic activity; type 1 predominate in the human anal sphincter, while cats and rabbits predominantly contain type 2 or fast-twitch muscle fibers [21]. The voluntary contraction of external anal sphincter remains at maximum intensity for about 1 minute and then declined to baseline pressure values in about 3 minutes. Parks and associates found that action potentials are present at rest in patients after spinal cord transection, but were absent in those with tabes dorsalis. These observations show that the muscle tone at rest is regulated by a spinal reflex, in tabes this reflex is interrupted for the destruction of the afferent branch of the spinal reflex [61]. The afferent neurons that activate the reflex have not yet been identified with certainty, but seem likely to be related to receptors relaxation and elongated muscle cells of elevator ani [62]. This hypothesis is confirmed by the observation that rectal distension causes a marked increase in external anal sphincter and pelvic floor (especially muscle puborectal), probably as a result of the tension exerted on muscle receptors. In proctocolectomy (with ileo-anal anastomosis) muscle tone at rest of the external anal sphincter is not modified in an important way to confirm that the receptors are not in the rectum wall itself but in the context of the sphincter [47,51]. Already Duthie and Gairns, examining multiple histological sections of the rectum, found the presence of sensory endings only in the transitional mucosa of the rectum and anal canal. Receptors pressure and tension in the levator ani and external anal sphincter had been demonstrated previously [63]. On the contrary Ruhl and colleagues demonstrated that sacral dorsal roots contain some afferents from low-threshold mechanoreceptors located in the rectal wall and that these afferents monitor the filling state and the contraction level of the rectum [64,65]. Sensation within the anal canal is carried out by several types of sensory receptors, including free intraepithelial nerve endings (pain), Meissner

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corpuscles (touch), bulbs of Krause (cold), Pacini corpuscles and Golgi-Mazzoni corpuscles (pressure and tension), and genital corpuscles (friction) [63]. Despite an extensive network of nerves within the anal mucosa, anal continence does not rely heavily on input from these nerve endings. They are thought to play only a minor role in discrimination between the states of fecal matter. Thus, when this area is anesthetized, discrimination between solid and gas is impaired; however, continence is maintained [17,66]. The tonically active puborectalis muscle maintains the resting anorectal angle. Moreover, puborectalis contraction during a sudden rise in abdominal pressure reduces the anorectal angle, preserving continence. While cadaveric studies suggested the puborectalis was supplied by the pudendal nerve, electrophysiological stimulation studies in humans suggested this muscle is supplied, strictly ipsilaterally, by branches originating from the sacral plexus above the pelvic floor. Disruption of the puborectalis inevitably causes significant incontinence, underscoring the importance of this muscle in maintaining continence [21] Once the rectum is distended, the internal sphincter relaxes (rectoanal inhibitory reflex) and the external sphincter contracts maintaining continence during the period in which the fecal material reaches the anorectal transitional zone where they are thickened sensory receptors. If the distension of the rectum is high, the limit of adaptation, the endorectal pressure reach critical values such as to induce a total inhibition of the sphincter with a sense of urgency to defecation. If the time is right for defecation, the voluntary relaxation of external anal sphincter in combination with other physiological mechanisms enable flushing. Relaxation of the puborectalis sling produces a widening of the anorectal angle (normally 60-105°, increases to 140°) producing an unobstructed anal pathway which facilitates defecation. Adding the pressure of a Valsalva maneuver overcomes the resistance of the external sphincter and the pelvic floor descends. If the external anal sphincter receives inhibiting signals causing relaxation, the fecal bolus passes. Timing results from the balance of environmental factors acting through cortical inhibition and basic reflexes of the anorectum.

PHYSIOLOGIC TESTING Multiple techniques have been developed to assess the physiologic function of the pelvic floor, rectum, and sphincters. In conjunction with a detailed history and physical exam, these techniques should be used to assess and detail function, identify and locate a lesion, or solidify a diagnosis. The understanding of many

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aspects of the physiology of continence and defecation (mechanisms still imperfectly known) uses some instrumental methods such as manometry, electromyography and defecography, nerve stimulation testing, radiographic studies, including endorectal ultrasound and magnetic resonance imaging (MRI).

ANORECTAL MANOMETRY The anorectal manometry measures pressure in the anal canal to assess the sphincter muscles during rest and voluntary contraction; is the gold standard in diagnosis of functional anorectal disorders. Investigation is crucial in constipation, which often associated with an increase in pressure with a corresponding increase in rectal volumes and capacity, and in the fecal incontinence. Anal manometry becomes an indispensable complement to the morphological investigations, first of all's ultrasound. There is no one standardized method when performing anorectal manometry, and each method has advantages and disadvantages. This method allows detection of:

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baseline pressure profile. Is the evaluation of anal pressure at rest, that value can be obtained by measuring stationary probe to 4-6 channels arranged longitudinally 1 cm away from each other, the expression of the internal anal sphincter tone and allows the calculation of the functional length of the anal canal itself. It is expressed as the maximum pressure in mmHg at rest. The measurement can also be done with extraction at constant speed, a probe at 4-8 channels with radial layout. Using this device allows for a more homogeneous as maintaining constant speed of extraction of the probe. dynamic pressure profile. Compared to the previous stage, is to evaluate the pressure in the anal canal starting from 6 up to 1 cm from the anal verge during maximum voluntary contraction. Is defined in this way the maximum pressure reached maximum value as voluntary and its durability, is defined as "squeeze" the difference between maximum pressure and the pressure baseline. This measurement is an index function of the external sphincter, increases lasts for only a minute at most. Squeeze pressure serves only to prevent leakage when the rectal content is presented to the proximal anal canal ad inappropriate times.

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

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the Rectum Anal Inhibitory Reflex (RAIR) that is evoked through the use of a latex balloon, placed inside rectum and inflated with air. The minimal volume required to elicit the internal anal sphincter relaxation is defined. Normally a testing sequence of 10, 20,30,40 and 50 ml is enough to elicit the RAIR. However, in patients with megarectum much larger volumes may be needed. The internal anal sphincter should normally relax (decrease in pressure 10-15 mmHg) in response to a 30-40 ml balloon distention. The absence of the inhibitory recto-anal reflex for any volume is highly suggestive of Hirschsprung's disease. rectal volume sensory thresholds. The first volume of rectal distention that the patient can distinguish to the maximum tolerable volume is determined. Normal values are generally between 100 and 300 ml. Subjects young and constipated patients tend to have greater capacity than rectal elderly and patients with fecal incontinence. rectal compliance can be calculated by difference between the volumes of first sensation and maximum tolerable volume divided by the pressure difference (C = ΔV / ΔP). Rectal compliance refers to the amount of force required to distend the rectal wall. Rectal compliance is measured by inserting an ultrathin polyethylene bag into the rectum. Once in place, the bag is inflated to different volumes, and the pressures from the rectal wall are measured. Multiple measurements are taken and are plotted on a pressure-volume curve. The slope of this curve reflects the compliance of the rectum. There are 3 phases of the compliance curve. The first phase corresponds to the initial resistance and compliance of the rectal wall. The second phase is more compliant as evidenced by the increased volume with pressure changes and represents ‗‗adaptive relaxation‘‘ of the rectal wall. The last phase represents the terminal compliance of the rectal wall and is generally less compliant than the other phases. Urge of defecation occurs during the second phase of compliance. Multiple studies have analyzed the association between anorectal pathologies and rectal compliance findings, and there is still controversy regarding its utility. This technique is also highly variable because of variations in readings of the equipment, variations in patient‘s physiology, and interobserver variations in readings [17]. Excessive rectal compliance means that a large volume difference corresponds to a small change in pressure with a tendency to rectal bulging. In contrast, a low compliance leads to a significant increase in pressure in response to small volume changes. Compliance, as well as the rectal capacity, varies with age. The normal rectal compliance is

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generally 2-6 ml H2O/mmHg. The normal rectal compliance seems to depend on an intact nervous system and the inherent vitality muscolare. the sphincter length can be calculated by performing a stationary / slow or a rapid pull through of the sphincter. The high pressure zone (HPZ) defined as the length of the internal anal sphincter. The length of the HPZ is usually between 2 to 3 cm in women and 2.5 - 3.5 cm in men 1. The HPZ indicates the sphincter length. the push / strain maneuver, the external anal sphincter should normally relax during this maneuver the average resting tone of the anal canal in healthy adults is generally between 50 and 70 mmHg and is lower in older people without gender differences. the maximum resting pressure is usually measured at 1 to 2 cm cranial to anal margin1. The resting pressure in the anal canal is due to 55% - 60% to 3 internal sphincter, 25% - 30% to the external sphincter 4 and the remaining 15% of the maximum pressure at rest in a hemorrhoidal plexus [21]. vector volume. The pressure profile of the sphincter can also be studied by using a specific catheter with six to eight radially orientated channels; a so-called ―vector volume‖. The vector asymmetry index is calculated considering the total value of all the differences between the pressure of each canal minus the mean value of all pressures. This analysis can give additional information regarding the geometry of the sphincter. Possible deficiencies and asymmetries are shown on a three-dimensional picture. The symmetry of the pressure vectors can be quantified and expressed through an index of asymmetry. Its maximum value in healthy individuals is 10%. Sphincter injury generate a radial pressure gradient with a higher mean asymmetry index of 20% in sleep and contraction [7]. Damon et al have recently shown that an index of asymmetry in HPZ of ≥ 25% is related to combined sphincter defects (sensitivity 81% specificity 71%) and that the same index squeeze ≥ 25% is related to wide defects of the external sphincter (sensitivity 100% specificity 76%) [67].

Now recognized the undoubted utility of manometry in the diagnosis and treatment choices in the most "common" diseases anorectal new perspectives offers vector study for the best understanding of functional disorders. The threedimensional vectormanometry allows for an integrated mapping of the radial pressure profiles necessary for identification of pressure asymmetries in the canal anal that, in our experience, are significantly correlated to anal sphincter injures.

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In our study, fifty-seven patients, out of 387, complained of fecal incontinence; the rate of asymmetric patients (75,4%) was significantly higher in incontinent group rather than in continent subject (p20% and the difference between asymmetric patients rate in presence or in absence of rectal prolapse was statistically significant (p= 0.0446). Finally, 92/387 (24%) was suffering of obstructed defecation, 45,6% of patients of these had an asymmetry index > 20% and the difference between asymmetric patients rate in presence or in absence of obstructed defecation were not statistically significant (p= 0.6004). Several hypotheses have been suggested to explain this manometric finding such as a pudendal neuropathy or, more likely, a malfunction of the internal anal sphincter due to a sphincter distortion by the prolapse or intussusceptions [68]. In conclusion anal vector manometry, using vector analysis of resting and squeeze anal pressure, and vector asymmetric index scoring are effective tools complementary to anal ultrasonography and provide information on both function and integrity of the anal sphincters. Vector asymmetry index>20% correlates with fecal incontinence due to anal sphincter lesions. Therefore, the anal vector manometry may be useful as an independent method of screening for pregnant women at risk of sphincter injury and for patients undergoing anorectal surgery at risk for incontinence, like previous anorectal surgery or history of two or more previous vaginal deliveries.

Electromyography Although endoanal ultrasound and MRI have shown superiority over electromyography (EMG) for localization of sphincter defects and elimination of the need for painful probe placement and the need for ionizing radiation, EMG can be used as an alternative technique [17].

Defecography Defecography can be used to investigate several anorectal abnormalities. It can measure the anorectal angle, the position of the pelvic floor at rest or during Valsalva (perineal descent), the presence of a rectocele, rectal intussusception, and function, including the ability to expel rectal contents.

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Ultrasound Ultrasonography can evaluate anal sphincter integrity and augment manometry and assess anorectal angles and puborectalis function. Ultrasonography evaluates discontinuity in anal sphincters, indicating a prior injury that may be seen in up to 30% of postvaginal deliveries. The internal and external sphincters can be evaluated separately. Various angles are measured with the patient at rest and during maximal voluntary contraction of the puborectalis. Ultrasonography does have the advantage of avoiding exposure to radiation and allows for longer viewing time. Anal ultrasonography relies on the operator for accuracy, but in experienced hands, it can be the mainstay for anal anatomic investigations. In addition, it can provide information regarding the presence and location of anorectal abscess and fistula and staging of tumors [17].

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SYMPTOMS AND DIAGNOSIS In most cases the first symptoms of an anal fissure is an intense pain during defecation with continuous stimulation (tenesmus), accompanied by burning and itching. The pain may last only a few minutes but also persist for several hours. Classically the pain of the fissure occurs in three different times: the beginning, during the passage of stool is fairly acute, then there is a phase of "stalled", at which time the pain may even disappear altogether, but after a few minutes , come back stronger than ever persist for hours. These symptoms are known as "pain syndrome in three times of the anal fissure." The pain is both a consequence who cause of spasm. In some cases the pain is so intense that the patients, frightened by defecation, try to avoid it for several days, becoming even more constipated and making it even more painful than the next, inevitable, evacuation. Sometimes the pain and spastic contraction of the anal sphincter muscles extend to the front of the pelvic floor causing urinary symptoms (pain or difficulty urinating). Usually at the end of defecation may be a slight bleeding which consists of a streak of bright red blood on toilet paper or on the stool. It is, however, contained hemorrhage that has nothing to do with the most abundant associated with hemorrhoidal disease. Since in some cases the two diseases are associated, the presence of traces of blood may be due to the concomitant presence of hemorrhoids or other injuries.

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When the fissure secretes a considerable amount of serum can make the anus "wet" causing itching. The proctological visit includes accurate medical history, digital exploration of the anal canal and anus-proctoscopy. The specialist must first rule out other conditions such as hemorrhoids, cancer of the anus and rectum, inflammatory bowel disease, sexually transmitted diseases. The patient is best placed in the lateral Sims position on a flat table with his right hand retracting the right buttock as an aid to the examiner. The prone position in a "jack-knife" attitude, which offers excellent access to the perineum, requires a special bed proctology. Is appropriate to take the examination very gently, at first gently widening laterally to the perineal region to deploy the mucocutaneous junction and then put out the fissure, just inside the anus. Often the tear is visible, usually this is all that‘s needed to diagnose an anal fissure. The research of the anal fissure is facilitated by the presence, at the lower end, hemorrhoid- like thickening of the mucosa, called "sentinel pile." The rectal examination, when possible for painful, can confirm the site of pain and then the fissure and is also appreciable hypertonia of the sphincter. The digital examination and proctoscope can cause severe pain with inability to see the ulcer. In this case you will need to take the exam under sedation. It is advisable to make diagnosis of anal fissure by simple inspection, referring rectal and proctoscopy examinations until the symptoms are not resolved with medical treatment or until surgery to be done under anesthesia. In the case of fissures refractory to medical therapy or surgery, or in the case of atypical appearance or location biopsy should be made to exclude other diseases such as Crohn's disease, anal cancer or sexually transmitted diseases. In case of bleeding, depending on the chronicity of symptoms, correlation with physical findings, patient's age and the presence or absence of other risk factors for cancer, should be considered the appropriateness of an endoscopic examination of the colon. Only the anal manometry can confirm the presence of internal sphincter hypertonia. Furthermore, knowing the degree of hypertonia and the length of the sphincter is possible to calibrate the extent of sphincterotomy. Calibrated sphincterotomy may represent an effective and safe procedure for the treatment of chronic anal fissure

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[19] Parks AG. The surgical treatment of hemorrhoids. Br. J. Surg. 1955; 43: 337-42. [20] Gold DM, Bartram CI, Halligan S, Kamm MA, Kmiot WA. The quantification of normal anal canal anatomy and sphincter defects using three-dimensional endoanal sonography. Br. J. Surg. 1998; 85 (Suppl l): 1. [21] Bharucha A.E.: Pelvic floor: anatomy and function. Neurogastroenterol. Motil. (2006) 18, 507-519 [22] Goligher JC, Leacock AG, Brossy J. The surgical anatomy of the anal canal. Br. J. Surg. 1955; 43: 51-23. [23] Corman ML. Colon and rectal surgery.5th edition. JB Lippincott, Philadelphia, 2005. [24] Stoker J.: Anorectal and pelvic floor anatomy, Best Practice and Research Clinical Gastroenterology 23 (2009) 463–475. [25] Shaflk A. A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation. III. The longitudinal anal muscle: anatomy and role in anal sphincter mechanism. Invest. Urol. 1976; 13: 2719. [26] Shafik A, Gamal el-Din MA, el-Sibaei O, Abdel Hamid Z, el-Said B. Involuntary action of the external anal sphincter: manometric and electromyographic studies. Eur. Surg. Res. 1992; 24: 188-93. [27] Garavoglia M, Levi AC, Borghi F, Bargoni A. Considerazioni anatomochirurgiche sull‘apparato muscolare del canale anale. Minerva Chir. 1987; 42:1085-91. [28] Courtney H. Anatomy of the pelvic diaphragm and anorectal musculature as related to sphincter preservation in anorectal surgery. Am. J. Surg. 1950; 79: 155-61. [29] Garavoglia M, Borghi F, Levi AC. Arrangement of the anal striated musculature. Dis Colon Rectum 1993; 36:10-3. [30] Fowler R. Landmarks and legends of the anal canal. Aust. N. Z. J. Surg. 1957; 27:1-6. [31] Shafik A. A new concept on the anatomy of sphincter mechanism and the physiology of defecation. The external anal sphincter: a triple-loop System. Invest. Urol. 1975; 12: 412-8. [32] Dalley AF. The riddle of the sphincters. The morphophysiology of the anorectal mechanism reviewed. Am. Surg. 1987; 53: 298-301 [33] Ayoub SF. Anatomy of the external sphincter in man. Acta Anat. 1979; 105:25-31. [34] Oh C, Kark AE. Anatomy of the external sphincter. Br. J. Surg. 1972; 59: 717-721.

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[35] Shafik A. A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation. II. Anatomy of the levator ani muscle with special reference to puborectalis. Invest. Urol. 1975; 13:175-82. [36] Percy JP, Swash M, Neill ME, Parks AG. Electrophysiological study of motor nerve supply of pelvic floor. Lancet 1981; ii: 16-20. [37] Huber A, von Hochstetter A, Allgower M. Anatomy of the pelvic floor for translevatoric-transsphincteric operations. Am. Surg. 1987; 53: 247-52. [38] Shepherd JJ. Anorectal function. In Sircus W, Smith AN, Eds. Scientiflc foundations of gastroenterology. Heinemann, London, 1980. [39] Shafik A., Asaad S., Doss S.: The histomorphologic structure of the levator ani muscle and its functional significance. Int. Urogynecol. J. (2002) 13: 116-124. [40] Siddhart P, Ravo B. Colorectal neurovasculature and anal sphincter. Surg. Clin. N. Am. 1988; 68: 1185-96. [41] Netter FH. Atlante di anatomia. Chiba-Geigy, Varese, 1984. [42] Patricio J, Bemades A, Nuno D, Falcao F, Silvera L. Surgical anatomy of the arterial blood-supply of the human rectum. Surg. Radiol. Anat. 1988; 10: 71-8. [43] Stelzner F, Staubesand J, Machleidt H. Das corpus cavemosum recti die grundlage der inneren hamorrhoiden. Langenbecks Arch. Klin. Chr. 1962; 299:302-306. [44] Di Matteo G. Principi e tecniche nella chirurgia per cancro del retto sottoperitoneale. Collana Monografica Società Italiana dì Chinirgia, Roma, 1995. [45] Bauer JJ, Gelernt IM, Salky B, et al. Sexual dysfunction following proctocolectomy for benign disease of the colon and rectum. Ann. Surg. 1983;197:363–7. [46] Grigorescu BA, Lazarou G, Olson TR, et al. Innervation of the levator ani muscles: description of the nerve branches to the pubococcygeus, iliococcygeus, and puborectalis muscles. Int. Urogynecol. J. Pelvic Floor Dysfunct 2008;19:107–16. [47] Di Matteo Q. Principi e tecniche nella Chirurgia per cancro del retto sottoperitoneale. Collana Monografica della Società Italiana di Chirurgia, Roma, 1995. [48] Davis K., Kumar D.: Posterior pelvic floor compartment disorders. Best Pract. Res. Clin. Obstet .Gynaecol. 2005 Dec;19(6):941-958. [49] Arhan P, Faverdin C, Persoz B, Devroede G, Dubois F, Domie C. Relationship between viscoelastic properties of the rectum and pressure in man. J. Appl. Physiol. 1976; 41: 677-83.

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Michele Grande

[50] Arhan P, Devroede G, Persoz B, Faverdin C, Dornic C, Pellerin D. Response of the anal canal to repeated distension of the rectum. Clin. Invest. Med. 1979;2(2-3):83-8. [51] Yamada T, Alpers DH, Kaplowitz N, Laine L, Owyang C, Powell DW. Textbook of gastroenterology. 4th Edition. (Eds) Lippincott Williams and Wilkins, Philadelphia 2004. [52] Bennett RC, Duthie HL The functional importance of the internal anal sphincter. Br. J. Surg. 1964; 51: 355-9. [53] Shepherd JJ, Wright PG. The response of internal anal sphincter in man to stimulation of the presacral nerve. Am. J. Dig. Dis. 1968; 13: 421-5. [54] Duthie HL, Watts JM. Contribution of the external anal sphincter to the pressure zone in the anal canal. Gut. 1965; 6: 64-8. [55] Penninckx F., Lestar B., Kerremans R.: The internal anal sphincter: mechanisms of control and its role in maintaining anal continence. Baillieres Clin. Gastroenterol. (1992) 6: 193-214. [56] Duthie GS, Bartolo DC. Faecal continence and defecation. In coloproctology and the pelvic floor. Butterworth-Heinemann, Oxford, 1992. [57] Burleigh DE, D‘Mello A. Physiology and pharmacology of the internal anal sphincter. In Henry MM, Swash M, Eds. Coloproctology and pelvic floor. Butterworths, London, 1985. [58] .Mathers S. Neural control of the pelvic sphincters. In coloproctology and the pelvic floor. Butterworth-Heinemann, Oxford, 1992. [59] Freukner B, von Euler C. Influence of pudendal nerve block on the function of the anal sphincters. Gut. 1975; 16: 482-5. [60] Pency JP, Neill ME, Swash M, Parte AG. Electrophysiological study of motor nerve supply of pelvic floor. Lancet 1981; i: 16-9. [61] Parks AG, Porter NH, Melzak J. Experimental study of the reflex mechanism controlling the muscles of the pelvic floor. Dis. Colon Rectum 1962; 5: 407-11. [62] Phillips SF, Edwards D. Some aspects of anal continence and defecation. Gut. 1965; 6: 396-401. [63] Duthie HL, Gains FW. Sensory ending and sensation in the anal region of man. Br. J. Surg. 1960; 47: 585-9. [64] Ruhl A, Thewissen M, Ross HG, et al. Discharge patterns of intramural mechanoreceptive afferents during selective distension of the cat‘s rectum. Neurogastroenterol. Motil. 1998;10:219–25. [65] Gowers WR. The automatic action of the sphincter ani. Proc. R. Soc. Lond 1877;26: 77-82.

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[66] Cherry DA, Rothenberger DA. Pelvic floor physiology. Surg. Clin. North Am. 1988; 68:1217–30. [67] Mounier P, Mollard P. Control of the internal anal sphincter (manometric study with human subjects). Pflugers Archiv. 1977; 370: 233-9. [68] Damon H, Henry L, Roman S, Barth X, Mion F: Influence of rectal prolapsed on the asymmetry of the anal sphincter in patients with anal incontinence. BMC Gastroenterol 2003; 19: 3-23.

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In: Anal Fissure Editors: P. Sileri and A. L. Gaspari

ISBN: 978-1-61209-716-9 © 2012 Nova Science Publishers, Inc

Chapter 2

CHEMICAL SPHINCTEROTOMY Giovanni Milito and Federica Cadeddu The Department of Surgery, University Hospital Tor Vergata, Rome, Italy

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ABSTRACT Although the debate about optimum first-line therapy for chronic fissure continues, treatment is becoming increasingly medical. Chemical sphincterotomy is effective in decreasing symptoms, improving healing of chronic anal fissure and avoiding the risk of anal incontinence associated with surgical treatment. Glyceryl trinitrate, a nitric oxide donor, is the first medical agent used and is now a well established first-line treatment. However, some authors reported an high incidence of side effects with glyceryl trinitrate, particularly a severe headache in over 30% of patients, forcing some subjects to stop the treatment. Twice-daily application of 0.2 percent glyceryl trinitrate ointment and, besides, local application of calcium channel blockers to the distal anal canal and anal margin lowers anal resting pressure, increases local blood flow, decrease anal pain leading to fissure healing in over two thirds of patients according to some authors. Alternative medical therapies including α1-adrenoceptor antagonists (indoramin) cholinergic agonists (bethanechol) endogenous nitric oxide donors(L-arginine), and phosphodiesterase Inhibitors are being tested in an effort to avoid the side effects of nitroglicerine but remain at a developmental stage.

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Giovanni Milito and Federica Cadeddu All these non surgical treatments are discussed in the present chapter with a focus on chemical composition and mechanism of action of these agents, safety profile and surgical results reported in literature.

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INTRODUCTION Greater than 90% of acute anal fissures are of short duration and heal spontaneously or with simple measures. A high-fiber diet with an increased intake of water is recommended, laxatives may be used when required to soften constipated stool and warm sitz baths may offer symptomatic relief. Acute fissures that fail to heal become chronic fissures, which have traditionally been treated by surgery [1]. Chronicity is defined by both chronology and morphology. Most surgeons consider the persistence for 6 weeks as a reasonable cut-off to define a chronic anal fissure. Morphologically, chronic anal fissure is characterized by the presence of 1.visible transverse IAS fibers at the bottom of a fissure; 2. indurated edges; 3. sentinel pile 4. hypertropical anal papilla [2]. The presence of an anal fissure is reliably associated with an elevated intraanal pressure and decreased blood flow to the anoderm. The increased pressure is generated by hypertonicity of the internal anal sphincter that includes blood vessels to the anoderm. The main target of the treatment of anal fissure is the IAS spasm reduction, either by pharmacologic agents or performing sphincterotomy [1,2]. Traditionally, lateral internal sphincterotomy has been considered the gold standard treatment for chronic fissures, but this procedure requires anaesthesia and is associated with a noteworthy risk of incontinence. More recently, various pharmacologic agents have been shown to decrease resting anal pressure and promote fissure healing. This so-called chemical sphincterotomy has been used as first-line treatment for chronic anal fissure in many centres [1,3]. Chemical sphincterotomy is particularly suitable in presence of risk factors for incontinence (previous anorectal surgery, history of multiple vaginal deliveries, prior incontinence, inflammatory bowel diseases) when sphincterotomy for anal fissure generally has an additional risk. In case of pharmacologic therapy failure or fissures recurrence, when patients have high resting anal pressure, lateral internal sphincterotomy is the treatment of choice [3]. Topical 0.2% GTN ointment has been the first chemical agent used in clinical practice4. Subsequently other drugs have shown effective results with fewer side

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31

effects; an important advantage of these novel treatments is that by acting through different pathways, they may be effective in the 30% of cases in which GTN fails.

NITRATES

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In the gastrointestinal tract, NO mediates NANC evoked relaxation of the longitudinal and circular smooth muscle from the lower oesophageal sphincter, stomach, duodenum, small intestine and internal anal sphincter [5]. Loder et al [6] and Guillemot et al. [7,8] demonstrated that topically applied NTG causes a significant reduction in resting anal canal pressure of normal human beings. The recognition of nitric oxide as a neurotransmitter mediating relaxation of the internal anal sphincter (figures 1 and 2) led to the widespread use of organic nitrates in the treatment of chronic anal fissure [9]. Preparations of isosorbide dinitrate and GTN have been effective to treat chronic anal fissure. The proposed mechanism of action has been reduced anal sphincter pressure or a primary or secondary increase in anal blood flow.

Figure 1. NO neurons included in the myenteric plexus of the bowel.

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32

Giovanni Milito and Federica Cadeddu

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Figure 2. Pathways of the enteric nervous system: NO motor neurons inhibits muscle contraction.

GTN and isosorbide dinitrate act as nitric oxide donors, being metabolized at a cellular level to release this compound. In these situations NO evokes a membrane hyperpolarization. NANC-stimulated relaxation of gastrointestinal smooth muscle is associated with an initial rapid hyperpolarization (large amplitude) followed by a sustained hyperpolarization (small amplitude). NO appears to mediate the latter hyperpolarization. Nitric oxide mediates relaxation of the internal sphincter through the guanylyl cyclase pathway by increasing cyclic guanosine monophosphate levels within the smooth muscle cells [5,9]. Organic nitrates chemically represent esters of nitric acid (HNO3) with monoor polyhydric alcohols. Individual potency of organic nitrates is proportional to the number of nitrate groups per molecule and is a function of their lipophility. Organic nitrates differ in their pharmacokinetics from each other. GTN is eliminated at a much faster rate than isosorbide mononitrate but, despite this, steady state concentrations of GTN can be maintained by transdermal formulations. When applied as an ointment, the absorption amount usually exceeds skin permeability that determines how much drug reaches the plasma. Thus, variable skin permeability, difficulty in standardizing the surface area and continuous changes in concentration gradient between ointment and plasma, lead

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Chemical Sphincterotomy

to irregular absorption and fluctuating plasma concentrations of GTN and isosorbide dinitrate [11,12]. Several studies have investigated the effect of topical glyceryl trinitrate ointment and supported the use of 0.2 to 0.4 percent nitroglycerin ointment for the treatment of anal fissure. Healing rates range from 30% to 86% [13](chart 1). Chart 1. Results in literature of gliceril trinitrate for the treatment of chronic anal fissure Authors, year

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Loder et al, 1994[6] Oettlé, 1997[28] Lund and Scholefield, 1997[14] Carapeti et al, 1999[16] Brisinda et al, 1999[25] Kennedy et al, 1999[15] Zuberi et al, 2000[17] Altomare et, al, 2000[19] Richards et al 2000[32] Pitt et al, 2001[20]

Patients N 20 12

Agent 0,2 % GTN

Healing rate % NR 83

Headache % 10 0

38

0,2 % GTN

68

58

23 25 43 18

0,2 % GTN 0,2 % GTN 0,2 % GTN 0,2 % GTN

65 60 46 67

72 20 NR 72

59

0,2 % GTN

49

34

44 64

0,2 % GTN* 0,2 % GTN 0,0.1,0.2,0.4% GTN

29.5 41

20.5 64

Bailey et al, 2002[22]

304

Mishra et al, 2005[30]

20

0,2 % GTN*

30 at 4 weeks

NR

27

0,2 % GTN*

56

NR

50

0.2% GTN

34

311

0.2% GTN or AD

70 54.5 at 12 weeks

Brown CJ et al, 2007[34] Brisinda et al, 2007[26] Sileri et al, 2010[35]

50

*Randomized trial GTN versus lateral internal sphincterotomy; GTN gliceril trinitrate; NR not reported; AD anal dilatators.

Recently, Lund randomized 80 patients to 0.2 per cent GTN (twice daily for 8 weeks) or to placebo paste [14]. Healing rates were significantly higher in the GTN group (68 versus 8 per cent; P < 0.001), but headaches were common (58 versus 18 per cent). Differently, Kennedy et al [15] reported an healing rate of 46% in the GNT group versus 16% in the placebo arm. In the longer term, 35 per cent of patients were submitted to internal sphincterotomy.

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Giovanni Milito and Federica Cadeddu

Carapeti et al [16] from St Mark‘s Hospital randomized 70 patients to GTN or placebo using higher doses of GTN (three times daily for 8 weeks). After eight weeks fissure had healed in 67% of patients treated with GTN compared with 32% with placebo (p=0.008). Neither improvement of results nor increase of morbidity were detected. Recently Zuberi et al [17] compared GTN patches applied to the buttocks to topical 0.2% GTN and surgery in a randomized study. Forty-two consecutive patients with chronic anal fissure were randomized to 0.2% GTN ointment or 10mg nitroglycerin patch for 8 weeks and a 12 controls underwent surgery without significant difference in healing rate. Although the initial results of GNT treatment were promising, subsequently concerns over medium-term relapse, tachyphylaxis and morbidity have been raised [13, 18]. In a multicentre randomized Italian trial on 132 patients, Altomare, Milito and coworkers [19] failed to demonstrate the superiority of GTN (twice daily for 4 weeks) over placebo (49 versus 52 per cent). Besides, improvements in pain and anodermal blood flow, as well as a reduction in resting pressure, were demonstrated. Different studies have suggested explanations for the poor healing rates with GTN. In a recent retrospective trial Pitt reported an healing rate of 41% and a relapse rate of 50% in 64 patients 52. Two independent risk factors for failure to heal were found: the presence of a sentinel pile (P < 0.035) and a history of fissure longer than 6 months (P < 0,019)[20]. Furthermore, direct comparison of trials is complicated by heterogeneity of the topical preparations, different dosages and duration of treatment, selection criteria for chronic anal fissures, and the duration of symptoms before treatment. Recently Azarnoff et al [21] evaluated the quality of nitrate preparations and found that over 40% of samples analyzed did not meet the United States Pharmacopoeia specifications for potency and/or content uniformity when filling a prescription for 0.3 percent nitroglycerin ointment. Subpotent nitroglycerin ointment and/or not uniformly distributed nitroglycerin throughout the product are much less likely to relieve patients anal fissure pain, a severe and debilitating symptom that may affect their ability to work. In a randomized multicenter trial of ASCRS, Bailey et al [22] tried to find the optimal treatment schedule of GNT to achieve fissure healing. A randomized, double- blind study of intra-anally applied nitroglycerin ointment (Anogesic™) was conducted in 304 patients randomized to 0.0, 0.1, 0.2, 0.4 percent nitroglycerin ointment applied twice or three times per day up to eight weeks. Nitroglycerin ointment significantly and rapidly reduced the pain associated with

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chronic anal fissures; a 0.4% concentration (1.5 mg GTN) was the most effective. The healing rate was approximately 50 percent in each group including placebo. The most common side effects of nitrates are headache and hypotension. The incidence of moderate to severe headaches is up to 84% of patients. Headache is particularly evident at higher concentrations of the drug. Compliance can be improved if the patients are warned of headache as a side effect and told that it is often easily dealt with by simple analgesia before application of the ointment. However, compliance seems not to be significantly affected by headache and treatment drop-outs are uncommon [23, 24]. Anal burning as a result of treatment with nitroglycerin has also been reported [13]. There is a potential for methaemoglobinaemia but this side effect is rare after clinical doses. In some patients, abrupt withdrawal of nitrates may bring about rebound responses in several haemodynamic parameters.

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NITRATES VERSUS BOTULINUM TOXIN Since their introduction nitrates have been compared to surgical and medical agents in the treatment of chronic anal fissure. Botulinum toxin injection into anal sphincter is another therapeutic approach which have been used to treat chronic anal fissure and avoid the risk of permanent injury to the anal sphincter. In a study by Brisinda et al [25], 50 patients were randomized to receive 20 U of Botox, administered as two injections on each side of the anterior midline of the internal sphincter, or 0.2% nitroglycerine ointment. After 2 months, the fissures were healed in 24 of 25 patients (96%) in the botulinum toxin group and 15 of 25 patients (60%) in the GTN group. No patient in either group had fecal incontinence or suffered from relapse. Similarly, in a following larger experience, the authors randomized 100 adults to receive treatment with either type A botulinum toxin — 30 units Botox® or 90 units Dysport® — injected into the internal anal sphincter or 0.2 percent nitroglycerin ointment applied three times daily for eight weeks. After two months, healing rate in botulinum arm was 92 percent versus 70 percent in the nitroglycerin group (P =0.009). Twenty patients — 3 in the botulinum toxin group and 17 in the nitroglycerin group (P